Preeclampsia is a severe pregnancy-related disease that is found in 3%-5% of pregnancies worldwide and is primarily related to the decreased proliferation and invasion of trophoblast cells and abnormal uterine spiral artery remodelling. However, studies on the pathogenesis of placental trophoblasts are insufficient, and the aetiology of PE remains unclear. Here, we report that endothelial protein C receptor (EPCR), a transmembrane glycoprotein, was down-regulated in placentas from preeclamptic patients. Moreover, lack of EPCR significantly reduced the trophoblast cell proliferation, invasion and tube formation capabilities. Microscale thermophoresis analysis showed that EPCR directly bound to protease-activated receptor 1 (PAR-1), a G protein-coupled receptor. This change resulted in a substantial reduction in active Rac1 and caused excessive actin rearrangement. Our findings reveal a previously unidentified role of EPCR in the regulation of trophoblast proliferation, invasion and tube formation through promotion of actin polymerization, which is required for normal placental development.

This study was aimed to explore the differential expression of long noncoding RNAs (lncRNA)-PCAT1, miR-145-5p and TLR4 in osteogenic differentiation via the Toll-like receptor (TLR) signalling pathway and consequently determine the potential molecular mechanism. The mRNAs and pathways related to the osteogenic differentiation in human adipose-derived stem cells (hADSCs) were analysed by bioinformatics. The MiRanda and TargetScan database were employed to detect the potential binding sites of miRNAs on lncRNAs and mRNAs. The differential expression of lncRNA-PCAT1, miR-145-5p and TLR4 were detected by qRT-PCR. Rrelated protein expression was analysed by Western blot. The targeted relationships between lncRNA-PCAT1, miR-145-5p and TLR4 were verified by dual-luciferase reporter assay. Alkaline phosphatase (ALP) activity and ARS staining assays were used to measure the impacts exerted by lncRNA PCAT1, miR-145-5p and TLR4 mRNA on osteogenic differentiation. After the induction of osteoblast differentiation, the expression of lncRNA-PCAT1 and TLR4 increased, while the expression of miR-145-5p decreased. Dual-luciferase reporter assay confirmed the targeted relationship between lncRNA-PCAT1, miR-145-5p, and TLR4. LncRNA-PCAT1 negatively regulated miR-145-5p and positively regulated TLR4. Knockdown of lncRNA-PCAT1 or TLR4 decreased the expression of osteogenic differentiation-related proteins, reduced the ALP and ARS levels and the activity of the TLR signalling pathway. MiR-145-5p could reverse the effects of PCAT1 and TLR4 in hADSCs osteogenic differentiation. LncRNA-PCAT1 negatively regulated miR-145-5p, which promoted TLR4 expression to promote osteogenic differentiation by activating the TLR signalling pathway.

The aim of this study is to identify potential biomarker of tuberculosis (TB) and determine its function. Differentially expressed mRNAs(DEGs) were selected from a blood database GSE101805, and then, 30 key genes were screened using STING, Cytoscape and further functionally enriched. We then found that only 6 of 13 genes related to ubiquitination (the first in the functional enrichment) were increased significantly. ROC analysis showed that UBE2L6, among 6 genes, had the highest diagnostic value, and then, we found that it also had mild value in differential diagnosis. Moreover, our analysis showed that UBE2L6 may be upregulated by type I interferon, which was further confirmed by us. In addition, we also found that UBE2L6 inhibits the apoptosis of Mycobacterium tuberculosis(Mtb)infected macrophages. Subsequently, we discovered that miR-146a-5p, which may target UBE2L6, is reduced in peripheral blood mononuclear cells (PBMC) and plasma of TB, and it also had certain diagnostic efficiency(AUC=0.791). In brief, we demonstrated that UBE2L6 as well as miR-146a-5p is a potential biomarker for TB and UBE2L6,which may also plays important role in TB by, at least, modulating Mtb-infected macrophage apoptosis.

Cardiomyocyte apoptosis is the main reason of cardiac injury after myocardial ischaemia-reperfusion (I/R) injury (MIRI), but the role of p300/CBP-associated factor (PCAF) on myocardial apoptosis in MIRI is unknown. The aim of this study was to investigate the main mechanism of PCAF modulating cardiomyocyte apoptosis in MIRI. The MIRI model was constructed by ligation of the rat left anterior descending coronary vessel for 30 min and reperfusion for 24 h in vivo. H9c2 cells were harvested after induced by hypoxia for 6 h and then reoxygenation for 24 h (H/R) in vitro. The RNA interference PCAF expression adenovirus was transfected into rat myocardium and H9c2 cells. The area of myocardial infarction, cardiac function, myocardial injury marker levels, apoptosis, inflammation and oxidative stress were detected respectively. Both I/R and H/R remarkably upregulated the expression of PCAF, and downregulation of PCAF significantly attenuated myocardial apoptosis, inflammation and oxidative stress caused by I/R and H/R. In addition, downregulation of PCAF inhibited the activation of NF-κB signalling pathway in cardiomyocytes undergoing H/R. Pretreatment of lipopolysaccharide, a NF-κB pathway activator, could blunt these protective effects of PCAF downregulation on myocardial apoptosis in MIRI. These results highlight that downregulation of PCAF could reduce cardiomyocyte apoptosis by inhibiting the NF-κB pathway, thereby providing protection for MIRI. Therefore, PCAF might be a promising target for protecting against cardiac dysfunction induced by MIRI.